ID RASH_RAT Reviewed; 189 AA. AC P20171; Q4KLL6; Q5RJJ8; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 31-OCT-2012, entry version 105. DE RecName: Full=GTPase HRas; DE AltName: Full=H-Ras-1; DE AltName: Full=Transforming protein p21; DE AltName: Full=c-H-ras; DE AltName: Full=p21ras; DE Contains: DE RecName: Full=GTPase HRas, N-terminally processed; DE Flags: Precursor; GN Name=Hras1; Synonyms=Hras; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=87064453; PubMed=3023901; RA Ruta M., Wolford R., Dhar R., Defeo-Jones D., Ellis R.W., RA Scolnick E.M.; RT "Nucleotide sequence of the two rat cellular rasH genes."; RL Mol. Cell. Biol. 6:1706-1710(1986). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Thymus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-37. RX PubMed=3027702; DOI=10.1073/pnas.84.3.774; RA Damante G., Filetti S., Rapoport B.; RT "Nucleotide sequence and characterization of the 5' flanking region of RT the rat Ha-ras protooncogene."; RL Proc. Natl. Acad. Sci. U.S.A. 84:774-778(1987). RN [4] RP ISOPRENYLATION AT CYS-186, CLEAVAGE, AND METHYLATION AT CYS-186. RX MEDLINE=88263004; PubMed=3290900; DOI=10.1073/pnas.85.13.4643; RA Clarke S., Vogel J.P., Deschenes R.J., Stock J.; RT "Posttranslational modification of the Ha-ras oncogene protein: RT evidence for a third class of protein carboxyl methyltransferases."; RL Proc. Natl. Acad. Sci. U.S.A. 85:4643-4647(1988). RN [5] RP INTERACTION WITH PLCE1, AND MUTAGENESIS OF ASN-26; THR-35; GLU-37; RP ASP-38; TYR-40; GLN-61 AND CYS-186. RX MEDLINE=21099252; PubMed=11179219; DOI=10.1093/emboj/20.4.743; RA Kelley G.G., Reks S.E., Ondrako J.M., Smrcka A.V.; RT "Phospholipase C(epsilon): a novel Ras effector."; RL EMBO J. 20:743-754(2001). RN [6] RP IDENTIFICATION IN A COMPLEX WITH BRAF; MAP2K1; MAPK3 AND RGS14, AND RP INTERACTION WITH RGS14. RX PubMed=19319189; DOI=10.1371/journal.pone.0004884; RA Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., RA Oestreich E.A., Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., RA Zylka M.J., Snider W.D., Siderovski D.P.; RT "Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras RT effector."; RL PLoS ONE 4:E4884-E4884(2009). RN [7] RP INTERACTION WITH RGS14, AND SUBCELLULAR LOCATION. RX PubMed=19878719; DOI=10.1016/j.cellsig.2009.10.005; RA Shu F.J., Ramineni S., Hepler J.R.; RT "RGS14 is a multifunctional scaffold that integrates G protein and RT Ras/Raf MAPkinase signalling pathways."; RL Cell. Signal. 22:366-376(2010). CC -!- FUNCTION: Ras proteins bind GDP/GTP and possess intrinsic GTPase CC activity. CC -!- ENZYME REGULATION: Alternate between an inactive form bound to GDP CC and an active form bound to GTP. Activated by a guanine CC nucleotide-exchange factor (GEF) and inactivated by a GTPase- CC activating protein (GAP). CC -!- SUBUNIT: Forms a signaling complex with RASGRP1 and DGKZ. In its CC GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. CC Interacts with RGL3 and RASSF5. Interacts with HSPD1. Interacts CC with PDE6D. Interacts with IKZF3. Interacts with GNB2L1 (By CC similarity). Found in a complex with at least BRAF, HRAS1, MAP2K1, CC MAPK3 and RGS14. Interacts (active GTP-bound form) with RGS14 (via CC RBD 1 domain). Interacts with PIK3CG; the interaction is required CC for membrane recruitment and beta-gamma G protein dimer-dependent CC activation of the PI3K gamma complex PIK3CG:PIK3R6 (By CC similarity). CC -!- SUBCELLULAR LOCATION: Cell membrane. Cell membrane; Lipid-anchor; CC Cytoplasmic side (By similarity). Golgi apparatus (By similarity). CC Golgi apparatus membrane; Lipid-anchor (By similarity). CC Note=Shuttles between the plasma membrane and the Golgi apparatus CC (By similarity). The active GTP-bound form is localized most CC strongly to membranes than the inactive GDP-bound form. CC -!- PTM: Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous CC cycle of de- and re-palmitoylation regulates rapid exchange CC between plasma membrane and Golgi (By similarity). CC -!- PTM: S-nitrosylated; critical for redox regulation. Important for CC stimulating guanine nucleotide exchange. No structural CC perturbation on nitrosylation. CC -!- PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14- CC prostaglandin-J2 is autocatalytic and reversible. It may occur as CC an alternative to other cysteine modifications, such as S- CC nitrosylation and S-palmitoylation (By similarity). CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family. CC -!- SEQUENCE CAUTION: CC Sequence=AAH86608.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; CC Sequence=AAH99130.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M13011; AAA42009.1; -; Genomic_DNA. DR EMBL; BC086608; AAH86608.1; ALT_INIT; mRNA. DR EMBL; BC099130; AAH99130.1; ALT_INIT; mRNA. DR EMBL; M15188; AAA42008.1; -; Genomic_DNA. DR IPI; IPI00196529; -. DR PIR; A25229; A25229. DR RefSeq; NP_001091711.1; NM_001098241.1. DR RefSeq; NP_001123913.1; NM_001130441.1. DR UniGene; Rn.102180; -. DR PDB; 3V4F; X-ray; 1.39 A; A=1-166. DR PDBsum; 3V4F; -. DR ProteinModelPortal; P20171; -. DR SMR; P20171; 1-166. DR MINT; MINT-4996514; -. DR STRING; P20171; -. DR PRIDE; P20171; -. DR GeneID; 293621; -. DR KEGG; rno:293621; -. DR UCSC; RGD:2827; rat. DR CTD; 3265; -. DR RGD; 2827; Hras. DR eggNOG; COG1100; -. DR HOGENOM; HOG000233973; -. DR HOVERGEN; HBG009351; -. DR InParanoid; P20171; -. DR KO; K02833; -. DR OMA; CMSCRCV; -. DR Reactome; REACT_111984; Signal Transduction. DR NextBio; 636547; -. DR Genevestigator; P20171; -. DR GermOnline; ENSRNOG00000016611; Rattus norvegicus. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB. DR GO; GO:0003924; F:GTPase activity; IEA:InterPro. DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Compara. DR GO; GO:0006915; P:apoptotic process; IMP:RGD. DR GO; GO:0007050; P:cell cycle arrest; IEA:Compara. DR GO; GO:0008283; P:cell proliferation; IEA:Compara. DR GO; GO:0090398; P:cellular senescence; IEA:Compara. DR GO; GO:0006897; P:endocytosis; IEA:Compara. DR GO; GO:0008629; P:induction of apoptosis by intracellular signals; IEA:Compara. DR GO; GO:0031575; P:mitotic cell cycle G1/S transition checkpoint; IEA:Compara. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Compara. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara. DR GO; GO:0045740; P:positive regulation of DNA replication; IMP:RGD. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Compara. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:RGD. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Compara. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Compara. DR GO; GO:0035022; P:positive regulation of Rac protein signal transduction; IEA:Compara. DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara. DR GO; GO:0051291; P:protein heterooligomerization; IPI:RGD. DR GO; GO:0007265; P:Ras protein signal transduction; IMP:RGD. DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Compara. DR GO; GO:0032228; P:regulation of synaptic transmission, GABAergic; IEA:Compara. DR GO; GO:0035176; P:social behavior; IEP:RGD. DR GO; GO:0051146; P:striated muscle cell differentiation; IEA:Compara. DR GO; GO:0008542; P:visual learning; IEA:Compara. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR020849; Small_GTPase_Ras. DR PANTHER; PTHR24070; PTHR24070; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00173; RAS; 1. DR TIGRFAMs; TIGR00231; small_GTP; 1. DR PROSITE; PS51421; RAS; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell membrane; Complete proteome; KW Golgi apparatus; GTP-binding; Lipoprotein; Membrane; Methylation; KW Nucleotide-binding; Palmitate; Prenylation; Proto-oncogene; KW Reference proteome; S-nitrosylation. FT CHAIN 1 186 GTPase HRas. FT /FTId=PRO_0000043000. FT INIT_MET 1 1 Removed; alternate (By similarity). FT CHAIN 2 186 GTPase HRas, N-terminally processed. FT /FTId=PRO_0000326479. FT PROPEP 187 189 Removed in mature form (By similarity). FT /FTId=PRO_0000043001. FT NP_BIND 10 17 GTP. FT NP_BIND 57 61 GTP. FT NP_BIND 116 119 GTP. FT REGION 166 185 Hypervariable region. FT MOTIF 32 40 Effector region. FT MOD_RES 1 1 N-acetylmethionine; in GTPase HRas; FT alternate (By similarity). FT MOD_RES 2 2 N-acetylthreonine; in GTPase HRas, N- FT terminally processed (By similarity). FT MOD_RES 118 118 S-nitrosocysteine (By similarity). FT MOD_RES 186 186 Cysteine methyl ester. FT LIPID 181 181 S-palmitoyl cysteine (By similarity). FT LIPID 184 184 S-(15-deoxy-Delta12,14-prostaglandin J2- FT 9-yl)cysteine; alternate (By similarity). FT LIPID 184 184 S-palmitoyl cysteine; alternate. FT LIPID 186 186 S-farnesyl cysteine. FT MUTAGEN 26 26 N->G: Interacts and partially stimulates FT PLCE1; when associated with L-61. FT MUTAGEN 35 35 T->S: No interaction and stimulation of FT PLCE1; when associated with L-61. FT MUTAGEN 37 37 E->G: Reduced interaction and stimulation FT of PLCE1; when associated with L-61. FT MUTAGEN 38 38 D->N: Reduced interaction and stimulation FT of PLCE1; when associated with L-61. FT MUTAGEN 40 40 Y->C: No interaction and stimulation of FT PLCE1; when associated with L-61. FT MUTAGEN 61 61 Q->L: Constitutively active. FT Constitutively interacts and stimulates FT PLCE1 phospholipase activity. Reduced FT interaction and stimulation of PLCE1; FT when associated with G-37 and N-38. No FT interaction and stimulation of PLCE1; FT when associated with S-35 and C-40. FT Interacts and partially stimulates PLCE1; FT when associated with G-26. Interacts but FT does not stimulate PLCE1; when associated FT with S-186. FT MUTAGEN 186 186 C->S: Interacts but does not stimulate FT PLCE1; when associated with L-61. FT CONFLICT 179 179 P -> L (in Ref. 1; AAA42009). FT STRAND 2 11 FT HELIX 16 25 FT STRAND 36 46 FT STRAND 49 58 FT HELIX 62 64 FT HELIX 68 72 FT STRAND 76 83 FT HELIX 87 91 FT HELIX 93 104 FT STRAND 111 116 FT HELIX 127 137 FT STRAND 141 143 FT TURN 146 148 FT HELIX 152 163 SQ SEQUENCE 189 AA; 21298 MW; EE6DC2D933E2856A CRC64; MTEYKLVVVG AGGVGKSALT IQLIQNHFVD EYDPTIEDSY RKQVVIDGET CLLDILDTAG QEEYSAMRDQ YMRTGEGFLC VFAINNTKSF EDIHQYREQI KRVKDSDDVP MVLVGNKCDL AARTVESRQA QDLARSYGIP YIETSAKTRQ GVEDAFYTLV REIRQHKLRK LNPPDESGPG CMSCKCVLS //